Mesenchymal Stem Cell-Derived Exosomes as a Double-Edged Sword: Balancing Inflammation and Immunosuppression in Human Papillomavirus-Infected Tissues.

Human papillomavirus (HPV) infection is the most common sexually transmitted viral infection, strongly associated with chronic inflammation and cervical cancer progression in women. Persistent HPV infection leads to an inflammatory microenvironment that promotes epithelial dysplasia and immune evasion. Exosomes derived from mesenchymal stem cells (MSC-exosomes) have emerged as promising immunomodulatory and anti-inflammatory agents. This review examines current evidence on the interaction between HPV-induced inflammation and exosomal signaling, with a particular focus on the therapeutic potential of MSC-exosomes. We discuss their roles in immune regulation, miRNA delivery, suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and epithelial regeneration. This anti-inflammatory effect may also impair local immune surveillance, potentially enabling viral persistence and progression to malignancy. In this narrative review, We reviewed PubMed, Scopus, and Web of Science articles published up to 2024 on MSC-exosome interactions with immune regulation in HPV-related diseases. Evidence suggests that while the anti-inflammatory effects of MSC-exosomes may help control HPV-associated inflammation, they can also impair local immune surveillance, potentially facilitating viral persistence and progression toward malignancy. This dual activity positions MSC-exosomes as a double-edged sword in the context of HPV pathogenesis. A deeper understanding of this paradox is essential for designing safer, context-specific MSC-based therapies that balance anti-inflammatory benefits with effective antiviral immune responses. Although direct studies on MSC-exosomes in HPV infections are limited, existing models suggest that they have the capacity to attenuate inflammation and restore cervical tissue homeostasis. This article also highlights knowledge gaps and future research directions necessary to develop MSC-exosome-based therapies for HPV-related cervical diseases.